rs10872670

Variant names:

• chr6-151348740-A-G
• rs10872670
• NM_005100.4:c.349A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000402676.7(AKAP12):​c.349A>G​(p.Lys117Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.774 in 1,590,998 control chromosomes in the GnomAD database, including 474,860 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.76 (42023 hom., cov: 21)
  • Exomes 𝑓: 0.78 (432837 hom.)
• Consequence: AKAP12 ENST00000402676.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.442
• Publications: 33 publications found

Genes affected

AKAP12 (HGNC:370): (A-kinase anchoring protein 12) The A-kinase anchor proteins (AKAPs) are a group of structurally diverse proteins, which have the common function of binding to the regulatory subunit of protein kinase A (PKA) and confining the holoenzyme to discrete locations within the cell. This gene encodes a member of the AKAP family. The encoded protein is expressed in endothelial cells, cultured fibroblasts, and osteosarcoma cells. It associates with protein kinases A and C and phosphatase, and serves as a scaffold protein in signal transduction. This protein and RII PKA colocalize at the cell periphery. This protein is a cell growth-related protein. Antibodies to this protein can be produced by patients with myasthenia gravis. Alternative splicing of this gene results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.87914E-7).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000402676.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKAP12	NM_005100.4	MANE Select	c.349A>G	p.Lys117Glu	missense	Exon 4 of 5	NP_005091.2
	AKAP12	NM_144497.2		c.55A>G	p.Lys19Glu	missense	Exon 2 of 3	NP_653080.1
	AKAP12	NM_001370346.1		c.34A>G	p.Lys12Glu	missense	Exon 2 of 3	NP_001357275.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKAP12	ENST00000402676.7	TSL:5 MANE Select	c.349A>G	p.Lys117Glu	missense	Exon 4 of 5	ENSP00000384537.2
	AKAP12	ENST00000253332.5	TSL:1	c.349A>G	p.Lys117Glu	missense	Exon 3 of 4	ENSP00000253332.1
	AKAP12	ENST00000354675.10	TSL:1	c.55A>G	p.Lys19Glu	missense	Exon 2 of 3	ENSP00000346702.6

Frequencies

GnomAD3 genomes AF: 0.759 AC: 110917 AN: 146178 Hom.: 41997 Cov.: 21

Gnomad AFR AF: 0.714

Gnomad AMI AF: 0.631

Gnomad AMR AF: 0.809

Gnomad ASJ AF: 0.822

Gnomad EAS AF: 0.622

Gnomad SAS AF: 0.659

Gnomad FIN AF: 0.801

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.782

Gnomad OTH AF: 0.777

GnomAD2 exomes AF: 0.754 AC: 186973 AN: 248104 AF XY: 0.748

Gnomad AFR exome AF: 0.705

Gnomad AMR exome AF: 0.828

Gnomad ASJ exome AF: 0.825

Gnomad EAS exome AF: 0.595

Gnomad FIN exome AF: 0.787

Gnomad NFE exome AF: 0.775

Gnomad OTH exome AF: 0.781

GnomAD4 exome AF: 0.776 AC: 1121038 AN: 1444722 Hom.: 432837 Cov.: 33 AF XY: 0.772 AC XY: 555037 AN XY: 718520

African (AFR) AF: 0.716 AC: 23436 AN: 32728

American (AMR) AF: 0.827 AC: 36427 AN: 44036

Ashkenazi Jewish (ASJ) AF: 0.834 AC: 21427 AN: 25698

East Asian (EAS) AF: 0.700 AC: 26455 AN: 37790

South Asian (SAS) AF: 0.657 AC: 56220 AN: 85514

European-Finnish (FIN) AF: 0.797 AC: 41580 AN: 52190

Middle Eastern (MID) AF: 0.794 AC: 4506 AN: 5676

European-Non Finnish (NFE) AF: 0.785 AC: 865080 AN: 1101876

Other (OTH) AF: 0.775 AC: 45907 AN: 59214

GnomAD4 genome AF: 0.759 AC: 110995 AN: 146276 Hom.: 42023 Cov.: 21 AF XY: 0.760 AC XY: 53938 AN XY: 70958

African (AFR) AF: 0.715 AC: 27990 AN: 39168

American (AMR) AF: 0.809 AC: 11624 AN: 14372

Ashkenazi Jewish (ASJ) AF: 0.822 AC: 2830 AN: 3442

East Asian (EAS) AF: 0.622 AC: 2954 AN: 4752

South Asian (SAS) AF: 0.659 AC: 2961 AN: 4490

European-Finnish (FIN) AF: 0.801 AC: 7811 AN: 9746

Middle Eastern (MID) AF: 0.800 AC: 224 AN: 280

European-Non Finnish (NFE) AF: 0.782 AC: 52498 AN: 67154

Other (OTH) AF: 0.778 AC: 1540 AN: 1980

Alfa AF: 0.769 Hom.: 164111

Bravo AF: 0.752

TwinsUK AF: 0.780 AC: 2894

ALSPAC AF: 0.773 AC: 2981

ESP6500AA AF: 0.698 AC: 3076

ESP6500EA AF: 0.787 AC: 6767

ExAC AF: 0.747 AC: 90652

Asia WGS AF: 0.647 AC: 2249 AN: 3476

EpiCase AF: 0.780

EpiControl AF: 0.783

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.7
DANN	Benign	0.60
DEOGEN2	Benign	0.012	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.16	T
MetaRNN	Benign	7.9e-7	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.46	N
PhyloP100		0.44
PrimateAI	Benign	0.30	T
PROVEAN	Benign	1.2	N
REVEL	Benign	0.042
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.015
MPC		0.23
ClinPred		0.0015	T
GERP RS		2.8
Varity_R		0.032
gMVP		0.015
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10872670; hg19: chr6-151669875; COSMIC: COSV53577250;